Oct 12, 2023
CBS gene; Another main pathway of homocysteine metabolism is the gene encoding the vitamin B6-dependent enzyme cystathionine β-synthase (CBS), which converts homocysteine to serine and cystathionine (Tilley, M. M. et al., 2011). CBS (Cystathionine β-synthase) catalyzes the first step of transsulfuration and contains the heme cofactor. This heme cofactor acts as a redox sensor and uses S-adenosylmethionine (SAM) as an activator (Kraus et al.1998; Barbara 2011). CBS enzyme deficiency causes homocystinuria, a hereditary autosomal recessive metabolic disease that leads to increased homocysteine plasma concentrations (Shi et al., 2015). Hyperhomocysteinemia is a risk factor for cardiovascular diseases.
|
CBS |
||||
|
Genes |
rs |
Minor Allele |
Minor Allele Description |
Reference |
|
CBS 360 |
rs1801181 |
C |
High relative risk for homocysteinemia. |
|
|
CBS 699 |
rs234706 |
G |
High relative risk for homocysteinemia. |
|
|
CBS |
rs2851391 |
T |
Increased relative risk for homocysteinemia. |
|
|
CBS |
rs5742905 |
C |
Increased relative risk for homocysteinemia. |
|
The table above includes CBS genes and polymorphisms that are involved in the transsulfuration pathway. Variants that reduce CBS enzyme activity cause homocysteniemia.
|
CBS |
||||
|
Genes |
rs |
Minor Allele |
Minor Allele Description |
Reference |
|
CBS 360 |
rs1801181 |
T |
High relative risk for increased enzyme activity. |
(Li et al., 2013) |
|
CBS 699 |
rs234706 |
A |
High relative risk for increased enzyme activity. |
(Li et al., 2013) |
The table above includes CBS genes and polymorphisms that are involved in the transsulfuration pathway. In a study on non-Hodgkin lymphoma (NHL) risk, the rs234706 homozygous TT genotype in CBS was associated with a reduced risk of NHL compared with CC. This decrease was observed with the intake of methionine, folate and vitamin B6 in the diet. This shows that these nutritional ingredients act as cofactors. The increase in the risk of NHL was observed in the homozygous variant genotype (TT versus CC) (C>T) in CBS (rs1801181) (Li et al., 2013). Increased homocysteine is observed in various psychological disorders such as depression, bipolar, and schizophrenia. In a study conducted on 120 bipolar patients, the CBS (rs5742905) gene was found to be related to bipolar (Permoda et al., 2014). In another study, CBS (rs5742905) TT was associated with hyperactivity and impulsivity (Saha et al., 2017). In a meta-analysis study, it was reported that the risk of stroke increased in those with CBS T833C (rs5742905) genetic polymorphism and that the C allele was a risk factor (Ding et al.2012). In a study looking at CBS rs2851391, an increased risk of CHD was observed in terms of congenital heart diseases compared to the offspring of mothers with the TT genotype and the offspring of mothers with the CC genotype. It was observed that if mothers with the CBS rs2851391 risk genotype (CT/TT) consumed fried, barbecued or harmful foods, the risk of CHD of the offspring increased, and on the contrary, when mothers with the rs2851391 CC genotype consumed foods such as fish, meat, eggs and fresh fruit, the risk of CHD of the offspring decreased. The rs2851391 mutant variant is associated with hyperhomocysteinemia and abnormal DNA methylation because it causes reduced enzyme activity (Li et al. 2021).
REFERENCE
Renga Barbara (2011).Hydrogen Sulfide Generation in Mammals: The Molecular Biology of Cystathionine-β-Synthase (CBS) and Cystathionine-γ-Lyase (CSE). Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy) (Discontinued), Volume 10, Number 2, pp. 85-91(7). https://pubmed.ncbi.nlm.nih.gov/21275900/
Jan P. Kraus , Jana Oliveriusová 2, Jitka Sokolová, Eva Kraus et al(1998). The Human Cystathionine β-Synthase (CBS) Gene: Complete Sequence, Alternative Splicing, and Polymorphisms. Genomics Volume 52, Issue 3,Pages 312-324. https://pubmed.ncbi.nlm.nih.gov/9790750/
Hui Shi, Shiwei Yang, Yan Liu,Peng Huang,Ning Lin,Xiaoru Sun et al. (2015).Study on Environmental Causes and SNPs of MTHFR, MS and CBS Genes Related to Congenital Heart Disease. Published: https://doi.org/10.1371/journal.pone.0128646
Yihuan Li, Jingyi Diao, Jinqi Li, Liu Luo et al.(2021). Association of maternal dietary intakes and CBS gene polymorphisms with congenital heart disease in offspring. International Journal of Cardiology 322;121–128. https://pubmed.ncbi.nlm.nih.gov/32800907/
Rui Ding,Shilei Lin,Daojun Chen.(2012). The association of Cystathionine β Synthase (CBS) T833C polymorphism and the risk of stroke: A meta-analysis.Journal of the Neurologıcal Scıences,Volume 312, Issue 1-2, P26-30. https://pubmed.ncbi.nlm.nih.gov/21917271/
Tanusree Saha, Mahasweta Chatterjee , Swagata Sinha, Usha Rajamma, Kanchan Mukhopadhyay.(2017). Components of the folate metabolic pathway and ADHD core traits: an exploration in eastern Indian probands. J Hum Genet;62(7):687-695. doi: 10.1038/jhg.2017.23. https://pubmed.ncbi.nlm.nih.gov/28250422/
Agnieszka Permoda-Osip; Monika Dmitrzak-Weglarz; Joanna Hauser; Janusz K. Rybakowski.(2014). Are Genes Connected with Homocysteine Metabolism Associated with Bipolar Disorder? Neuropsychobiology 69 (2): 107–111. https://pubmed.ncbi.nlm.nih.gov/24577139/
Tilley, M. M., Northrup, H., & Au, K. S. (2011). Genetic Studies of the Cystathionine Beta-Synthase Gene and Myelomeningocele. Birth Defects Research. Part A, Clinical and Molecular Teratology, 94(1), 52. https://doi.org/10.1002/bdra.22855